Thrombomodulin-modified Thrombin Generation Assay (TGA-TM) in Patients With Critical Infections

NCT ID: NCT04356144

Last Updated: 2021-03-23

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 58 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-04-15
• Study Completion Date: 2021-02-01

Brief Summary

Inflammation and abnormalities in laboratory coagulation tests are inseparably tied. For example, coagulation abnormalities are nearly universal in septic patients. Coagulation disorders have also been reported in many patients with severe courses of Coronavirus disease 2019 (Covid-19). But it is difficult to assess these changes. Global coagulation tests have been shown to incorrectly assess in vivo coagulation in patients admitted to intensive care units. But other tests are available. Thrombin generation assay (TGA) is a laboratory test which allows the assessment of an individual's potential to generate thrombin. But also in conventional TGA the protein C system is hardly activated because of the absence of endothelial cells (containing natural thrombomodulin) in the plasma sample. Therefore the investigators add recombinant human thrombomodulin to a conventional TGA. Thereby the investigators hope to be able to depict in vivo coagulation more closely than global coagulation tests do.

Conditions

Disseminated Intravascular Coagulation; Critical Illness; Sars-CoV2; Viral Infection; Coagulation Disorder, Blood; Covid19

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Critical infection

Patients with signs of infection with SARS-CoV-2 or already diagnosed infection with SARS-CoV-2 admitted to the ICU

Thrombin Generation Assay (TGA)

Intervention Type: DIAGNOSTIC_TEST

TGA via a fluorimetric module. Coagulation cascade is activated upon addition of different concentrations of tissue factor and phospholipids. The fluorogenic substrate Z-Gly-Gly-Arg-AMC (ZGGR-AMC) is cleaved by formed thrombin over time. By plotting the changes in fluorescence as a function of time (cnt/min), it depicts the "Thrombin Generation Curve" (thrombin generated - plotted against time). The area under the thrombin curve is defined as the endogenous thrombin potential (ETP).

Thrombomodulin Modified Thrombin Generation Assay (TGA-TM)

Intervention Type: DIAGNOSTIC_TEST

Recombinant Human Thrombomodulin (TM) is added to the conventional TGA. When recombinant TM is added, the protein C system is fully activated and therefore the ETP obtained reflects both the anti- and procoagulant factors.

Interventions

Thrombin Generation Assay (TGA)

TGA via a fluorimetric module. Coagulation cascade is activated upon addition of different concentrations of tissue factor and phospholipids. The fluorogenic substrate Z-Gly-Gly-Arg-AMC (ZGGR-AMC) is cleaved by formed thrombin over time. By plotting the changes in fluorescence as a function of time (cnt/min), it depicts the "Thrombin Generation Curve" (thrombin generated - plotted against time). The area under the thrombin curve is defined as the endogenous thrombin potential (ETP).

Intervention Type: DIAGNOSTIC_TEST

Thrombomodulin Modified Thrombin Generation Assay (TGA-TM)

Recombinant Human Thrombomodulin (TM) is added to the conventional TGA. When recombinant TM is added, the protein C system is fully activated and therefore the ETP obtained reflects both the anti- and procoagulant factors.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Admission to ICU
• Clinical signs of infection with SARS-CoV-2 or already diagnosed infection with SARS-CoV-2
• Neutrophil-Lymphocyte Ratio (NLR) >3

Exclusion Criteria

• Intake of oral anticoagulants or any kind of parenteral therapeutic anticoagulation prior to ICU admission
• Congenital coagulation disorder
• Treatment with Prothrombin complex concentrate (F. II, VII, IX, X) or activated Prothrombin complex within past 48 hours
• Treatment with recombinant factor VIIa (e.g. eptacog alfa) within past 48 hours
• Treatment with recombinant protein C within past 48 hours
• Active bleeding
• Acute myocardial infarction
• HIV infection
• Chronic pancreatitis
• Liver cirrhosis

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical Scientific Fund of the Mayor of Vienna

OTHER

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Lukas Infanger

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Medical University Vienna

Vienna, , Austria

Countries

Austria

Other Identifiers

TGA-TM-Critical-2019

Identifier Type: -

Identifier Source: org_study_id